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Title: Comparative models of transplant and non-transplant human kidney disease
Author: Kubal, Chandrashekhar
ISNI:       0000 0004 2727 4781
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2012
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Late kidney transplant losses along with chronic kidney disease in non-renal solid organ transplantation pose major problem in this field. To address this I compared ischaemia, interstitial scarring and inflammation on the renal biopsies from failing renal transplants and chronic kidney disease outside renal transplantation using native CKD as a control group. For matched renal function, a similar degree of interstitial scarring was observed across the three study groups. Ischaemia was predominant in failing renal transplants; conversely inflammation was predominant in native CKD. The relationship between macrophages and endothelial cells indicated that, despite a lower macrophage load, there may be an allogeneic impact of macrophages on endothelial cells. In the biopsies from CKD, mRNA levels for iNOS, arginase, CX3CL1, BCL-2, MCP-1/CCL2 and FSP-1 were increased in association with an increasing macrophage load. Macrophage load correlated positively with arginase/iNOS mRNA ratio, suggesting M2 phenotypic transformation of the macrophages. Co-localization studies, demonstrated an increased number of macrophages within 5 microns from endothelial cells in failing renal transplants when compared to chronic kidney disease. Further studies directed towards manipulating macrophage-endothelial cell interaction may be potentially beneficial in improving the longevity of renal transplants.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General)